Innate Lymphocytes-L13 Flashcards
People lacking NK cells are susceptible to what types of illness?
-Herpetic viruses
Two subsets of NK cells in humans
CD56 CD3- (dim and bright)
What attracts NK cells to the tissue from the circulation
-Chemoattractants–interferons
Safety features of NK cells
- Can only kill one target cell at a time and at a certain distance
- Sum of interactions between inhibitory receptors and activating receptors determines the decision to kill or not to kill
- Default is to remain inhibited
- NK cells are activated locally
Macrophage recruitment of NK cells
- Inflammatory cytokines recruit and stimulate NK cells
- NK cell and macrophage form a conjugate pair where IL12 and IL15 activate the NK cell
- NK cells proliferate and turn into effector NK cells secreting IFNy
- IFNy binds macrophages and activates them
- It’s a cycle
NK cell activation by dendritic cells
- IL15 activates
- When innate immunity has infection under control NK cells will limit DC
- Otherwise NK cells will promote DC differentiation and their migration to the lymph node to get the adaptive immune response going
NK cells express what special kinds of receptors?
- Toll like receptors: TLRs
- TLR 3,7,8
-TLR3
-Expressed by NK cells for dsRNA (viral)
TLR 7,8
-Expressed by NK cells for ssRNA
What senses MHC class 1 in NK cells for an inhibitory signal?
- KIR molecules
- CD94:NKG2A complexes
Nk cell effector function
- Selectively kill target cells in distress that down-regulate MHC class 1 molecules, or upregulate stress-induced self molecules
- Sums the inputs to decide if it needs to inhibit or activate
Activation of NK cells requirements
- Two signals from two or more activating receptors
- NKG2D is a common activating signal
- In the presence of IgG the Fc receptor can activate NK cells without help from another receptor
NKG2D
-Activating signal for NK cells
NK cell detection of self (the first detection)
- Via CD94: NKG2A receptor complex that detects the presence of MHC class 1 (HLA) based on HLA-E presentation of leader peptides from HLA-A, B, C
- Get turned on before KIRs in development
- Sends inhibitory signal
KIR
- Killer inhibitory receptors
- Another way for NK cells to detect self
- Direct recognition of HLA-A,B, C. No peptide recognition involved.
- Predominant self receptor after education
Education of NK cells
- A threshold of inhibitory signaling that NK activating receptors must overcome
- Basically setting a threshold of signals for activation
- Tells us how much Vav activation necessary to make NK cell active
NK cells in the control of CMV
- CMV will down regulate class 1 MHC and interferes with peptide presentation by HLA to avoid CD8 T cell response.
- BUT this makes them vulnerable to NK killing
- CD94:NKG2C is an activating complex
- This subset of NK cells expressing this complex expands and stays elevated throughout life (NK memory)
Uterine NK cells
- Control invasion of fetal trophoblast cells in the developing placenta
- Make angiogenic factors that promote vessel growth
- KIR2DL4:HLA-G interaction
Gamma delta T cells
- Plentiful in tissues, particularly in the gut
- Not a ton circulating in the blood
- Tissue homeostasis, surveillance, and repair
- Not MHC restricted
Vgamma9:Vdelta 2 T cells
- Recognize phosphoantigens presented on cell surfaces by CD277
- Promote inflammation that will lead the control of the infection
Vgamma4:Vdelta5 T cells
- Respond to CMV infected cells
- Upregulate EPCR which binds phospholipids
- Mediates inflammatory cytokine production
Vgamma:Vdelta1 T cells
-Recognize lipid antigens presented by CD1d
CD1s
Present mycobacterial lipids to gamma delta T cells which is important for control of leprosy and TB
NKT cells
- Express NK receptors like NKG2D
- Require signal from TCR and from a cytokine for activation
- Initiate inflammation
